3u78 | pdb_00003u78

E67-2 selectively inhibits KIAA1718, a human histone H3 lysine 9 Jumonji demethylase

spinqualitylabelsall models 3u78, resolution 2.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u78 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AKG, CL, E67, EDO, NI, SO4 Related: 3kva Gene: JHDM1D, KDM7, KIAA1718 (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed BIX-01294 and its analogs were originally identified and subsequently designed as potent inhibitors against histone H3 lysine 9 (H3K9) methyltransferases G9a and G9a-like protein. Here, we show that BIX-01294 and its analog E67 can also inhibit H3K9 Jumonji demethylase KIAA1718 with half-maximal inhibitory concentrations in low micromolar range. Crystallographic analysis of KIAA1718 Jumonji domain in complex with E67 indicated that the benzylated six-membered piperidine ring was disordered and exposed to solvent. Removing the moiety (generating compound E67-2) has no effect on the potency against KIAA1718 but, unexpectedly, lost inhibition against G9a-like protein by a factor of 1500. Furthermore, E67 and E67-2 have no effect on the activity against histone H3 lysine 4 (H3K4) demethylase JARID1C. Thus, our study provides a new avenue for designing and improving the potency and selectivity of inhibitors against H3K9 Jumonji demethylases over H3K9 methyltransferases and H3K4 demethylases. An Analog of BIX-01294 Selectively Inhibits a Family of Histone H3 Lysine 9 Jumonji Demethylases.,Upadhyay AK, Rotili D, Han JW, Hu R, Chang Y, Labella D, Zhang X, Yoon YS, Mai A, Cheng X J Mol Biol. 2011 Dec 29. PMID:22227394 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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